This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Functional neuroimaging with diffuse optical tomography (DOT) requires separation of functional cerebral hemodynamic changes from physiological regulation dynamics. We commonly observe physiological variability in DOT that correlates with physiological parameters such as blood pressure and heart rate but these physiological components of DOT are not well characterized. We have developed a nonlinear spatiotemporal forward model that incorporates cardiovascular and cerebral physiology and spatial structure of the human head to improve understanding of the physiological basis of DOT and to evaluate tomographic reconstruction methods. We use nonlinear, lumped parameter models of the systemic and cerebral circulatory systems. The cardiovascular model includes a pulsatile heart, circulation and a short-term regulatory system with arterial baroreflex, cardiopulmonary baroreflex and a neurological coupling between respiration and heart rate. Arterial blood pressure from the peripheral cardiovascular model drives our cerebral autoregulation and gas exchange model. The cerebral compartment includes circulation, interstitial and intracellular fluid spaces, CSF, gas transport, metabolic demands and autoregulation of cerebral blood flow. The physiological models are coupled to a structural model of the human head, which is based on segmentation of an anatomical MRI including scalp, skull, cerebral spinal fluid (CSF), grey and white brain matter. The physiological models are used to estimate the time-varying optical properties of each tissue type and then simulate optical measurements with a Monte Carlo solution to the radiative transport equation.